Columns used in liquid chromatography typically comprise a tubular body enclosing a porous chromatography media through which a carrier liquid flows, with separation taking place by material collection between the carrier liquid and solid phase of the porous media. Typically, the porous media is enclosed in the column as a packed bed, typically formed by consolidating a suspension of discrete particles, known as slurry that is pumped or poured or sucked into the column, usually from one end.
Consolidating of the slurry into a packed bed is achieved by compressing the slurry so that it is packed into a volume which is less than the volume that it would have occupied if it had sedimented under the influence of only gravity to form a sedimented bed. The efficiency of subsequent chromatographic separation relies strongly on the liquid distribution and collection system at the fluid inlet and outlet of the packed bed, and on the compression of the packed bed. If the compression of the compressed bed is too low then chromatographic separations performed on the bed suffer from “tailing”. If the compression of the compressed bed is too high then chromatographic separations performed on the bed suffer from “leading”. If the compression is optimum then the separation peaks formed during use exhibit neither leading nor tailing and are substantially symmetrical. The optimum degree of compression required for a column is determined experimentally for each column size (width or diameter), bed height and bed media.
Prior to any separation process, the bed has to be prepared starting from the slurry of particles that has to be introduced into the column. The process of bed formation is called ‘the packing procedure’ and a correctly packed bed is a critical factor influencing the performance of a column containing a packed bed. The goal of the packing procedure is to provide a bed compressed by the optimum amount of compression—the optimum compression factor. The height of the bed when it is optimally compressed is called the target compressed bed height. Large scale columns are preferably prepared by injecting into the column, through a central slurry nozzle, a predetermined volume of slurry having a specified concentration of media particles. Once the predetermined volume of slurry has been injected into the column it may be compressed by moving a movable adapter down the longitudinal axis of the column towards the bottom of the column, normally at a constant speed, e.g. 1 cm per minute. The excess liquid during this procedure is removed at the column outlet, while the particles are retained by means of a filter material, a so-called ‘bed support’, with pores too small to allow the particles to pass though. The packing process is complete once the packed bed has been compressed by the optimum amount. The packing process is considered as being successful if the compressed bed allows for a good and robust chromatographic performance quantified in terms of the residence time distribution over the bed. However, producing such an optimally compressed bed is not easy to achieve in practice. Bed packing has hitherto been regarded as an art rather than a science and the quality of the final packed bed is dependant on the skill of the operator controlling the filling of the column. One reason for this is that it is difficult to ensure that the actual slurry concentration fed in the column is exactly the same as the specified concentration used in the calculation of how much slurry should be fed into the column. Any difference between actual slurry concentration and the specified slurry concentration will result in the actual bed heath being different to the target bed height and/or the actual amount of compression of the bed being different from the specified compression. During filling and the subsequent packing of the column, the operator manually selects and adjusts the packing parameters such as flow rates, adapter speed of advancement and bed compression, and has to judge the point when the adapter starts compressing the bed. This point is used to calculate how much further the adapter must move in order to obtain the required amount of compression. Mistakes in the selection of any of these packing parameters may lead to a poorly performing column. It is particularly difficult to judge by eye when compression of the bed actually starts and a significant error at this point makes it impossible to obtain an optimally compressed bed.
As used herein and in the appended claims: the term “fluid system” is intended to designate the apparatus in which liquid is either introduced to or withdrawn from a cell at a zone approximately transverse the direction of flow through the cell. The term “cell” is intended to include the terms “vessel” and “column”, as well as any other structure utilised by practitioners of the separation arts, to effect a separation, and/or reaction, and/or catalysation, and/or extraction of components from an admixture by bringing the admixture into contact with solid or liquid exchange media, known as the packed bed. “Cross-sectional zone” (or region or portion) refers to a region within a cell bounded by cross sections of the cell-oriented transverse (typically approximately normal) the longitudinal direction of flow through the cell. “Longitudinal direction of flow” refers to the direction of flow from an inlet towards an outlet within a cell. “Longitudinal” is used consistently to designate the dominant flow path of fluid through a cell without regard to direction. “Flow connection system” refers to a system of channels or paths that connect two points in a fluid circuit. “Distribution system” refers to structures through which fluids are introduced to a cell and “collection system” refers to structures used to collect fluids from a cell, in each instance from a cross-sectional zone.
“Sedimented bed height” refers to the height of a bed of bed media particles which is obtained when a bed of media particles is formed after the bed media particles in a slurry of a liquid and media particles in a column are allowed to sediment under the influence of gravity only—such a bed is called a “sedimented bed”. “Consolidated bed height” refers to the height of a bed of bed media particles that is obtained when a bed of media particles is formed in a column while a slurry of media particles is forced to sediment under the influence of gravity and an additional downward force exerted on the bed particles, for example by the flow of fluid through the bed caused by the movement (for example, the descent) of a movable adapter towards the bed and/or liquid pumped or sucked through the bed—such a bed is called a “consolidated bed”. “Compressed bed height” refers to the height of a bed of bed media particles in a column that is obtained when a consolidated bed has been compressed, for example by contact with, and further movement of, a movable adapter or the like, or by pumping fluid through the column at a higher rate than that used during consolidation of the bed—such a bed is called a “compressed bed”.